247068-85-5

Basic information

• Product Name: 1-Pentanone, 2-aMino-4-Methyl-1-[(2R)-2-Methyloxiranyl]-, (2S)-, trifluoroacetate (9CI)
• Synonyms: 1-Pentanone, 2-aMino-4-Methyl-1-[(2R)-2-Methyloxiranyl]-, (2S)-, trifluoroacetate (9CI);(S)-2-aMino-4-Methyl-1-((R)-2-Methyloxiran-2-yl)pentan-1-one, trifluoroacetate;(2S)-2-AMino-4-Methyl-1-[(2R)-2-Methyloxiranyl]-1-pentanone trifluoroacetate;(S)-2-amino-4-methyl-1-((R)-2-methyloxiran-2-yl)pentan-1-one trifuoro acid salt;(2S)-2-Amino-4-methyl-1-[(2R)-2-methyloxiranyl]-1-pentanonetrifluoroacetat;-​(2R)​[(2s)​
• CAS NO: 247068-85-5
• Molecular Formula: C11H18F3NO4
• Molecular Weight: 285.2601296
• EINECS: 1592732-453-0
• Mol File: 247068-85-5.mol
• Article Data: 20

Chemical Properties

• Appearance: /
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: 1-Pentanone, 2-aMino-4-Methyl-1-[(2R)-2-Methyloxiranyl]-, (2S)-, trifluoroacetate (9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Pentanone, 2-aMino-4-Methyl-1-[(2R)-2-Methyloxiranyl]-, (2S)-, trifluoroacetate (9CI)(247068-85-5)
• EPA Substance Registry System: 1-Pentanone, 2-aMino-4-Methyl-1-[(2R)-2-Methyloxiranyl]-, (2S)-, trifluoroacetate (9CI)(247068-85-5)

Safety Data

• Hazardous Substances Data: 247068-85-5(Hazardous Substances Data)

Usage

Description

1-Pentanone, 2-aMino-4-Methyl-1-[(2R)-2-Methyloxiranyl]-, (2S)-, trifluoroacetate (9CI) is a complex organic compound that serves as an intermediate in the synthesis of Carfilzomib (C183460), a second-generation proteasome inhibitor. 1-Pentanone, 2-aMino-4-Methyl-1-[(2R)-2-Methyloxiranyl]-, (2S)-, trifluoroacetate (9CI) plays a crucial role in the development of a potent treatment for relapsed and refractory multiple myeloma, a type of blood cancer.

Uses

Used in Pharmaceutical Industry:
1-Pentanone, 2-aMino-4-Methyl-1-[(2R)-2-Methyloxiranyl]-, (2S)-, trifluoroacetate (9CI) is used as an intermediate compound for the production of Carfilzomib, a second-generation proteasome inhibitor. This application is significant because Carfilzomib is an essential treatment option for patients with relapsed and refractory multiple myeloma, a blood cancer that affects plasma cells. The compound's role in the synthesis of Carfilzomib highlights its importance in the development of innovative cancer therapies.

Upstream product

• 76-05-1 trifluoroacetic acid 
• 247068-82-2 tert-butyl ((2S)-4-methyl-1-((2R)-2-methyloxirane-2-yl)-1-oxopentan-2-yl)carbamate 
• 2018-66-8 Z-Leu-OH 
• 869487-76-3 (S)-benzyl (2,6-dimethyl-3-oxohept-1-en-4-yl)carbamate 
• 109075-73-2 benzyl (S)-[1-(N-methoxy-N-methylamino)-4-methyl-1-oxopentan-2-yl]carbamate 
• 13139-15-6 N-tert-butoxycarbonyl-L-leucine 
• 87694-50-6 N-(tert-butoxycarbonyl)-L-leucine-N'-methoxy-N'-methylamide 
• 247068-81-1 tert-butyl [(1S)-3-methyl-1-(2-methylpropyl)-2-oxobut-3-en-1-yl]carbamate 
• 61-90-5 L-leucine 
• 95084-25-6 (S)-2-dibenzylamino-4-methylpentanoic acid 
• 131150-36-2 (S)-2-(dibenzylamino)-N'-methoxy-4,N'-dimethylpentane amide 
• 1609959-47-8 tert-butyl N-[(2S)-1-(-2-methyloxirane-2-yl)-1-hydroxy-4-methylpentan-2-yl]carbamate 
• 1609959-45-6 tert-butyl N-[(4S)-3-hydroxy-2,6-dimethylhept-1-en-4-yl]carbamate 
• 16937-99-8 N-Boc-D-Leu 

Downstream Products

• 1262241-20-2 C₃₄H₅₃N₅O₆ 
• 247068-82-2 tert-butyl ((2S)-4-methyl-1-((2R)-2-methyloxirane-2-yl)-1-oxopentan-2-yl)carbamate 
• 868540-17-4 carfilzomib 
• 247068-84-4 (2S)-2-amino-4-methyl-1-[(2R)-2-methyloxiran-2-yl]pentan-1-one 

Relevant articles and documents

Acetylene functionalized BODIPY dyes and their application in the synthesis of activity based proteasome probes

The synthesis of three acetylene functionalized BODIPY dyes is described. These dyes are used to fluorescently modify an azido functionalized epoxomicin analogue employing the Huisgen 1,3-dipolar cycloaddition, resulting in a panel of fluorescent epoxomic

Macrocyclic Immunoproteasome Inhibitors as a Potential Therapy for Alzheimer's Disease

Previously, we reported that immunoproteasome (iP)-targeting linear peptide epoxyketones improve cognitive function in mouse models of Alzheimer's disease (AD) in a manner independent of amyloid β. However, these compounds' clinical prospect for AD is limited due to potential issues, such as poor brain penetration and metabolic instability. Here, we report the development of iP-selective macrocyclic peptide epoxyketones prepared by a ring-closing metathesis reaction between two terminal alkenes attached at the P2 and P3/P4 positions of linear counterparts. We show that a lead macrocyclic compound DB-60 (20) effectively inhibits the catalytic activity of iP in ABCB1-overexpressing cells (IC50: 105 nM) and has metabolic stability superior to its linear counterpart. DB-60 (20) also lowered the serum levels of IL-1α and ameliorated cognitive deficits in Tg2576 mice. The results collectively suggest that macrocyclic peptide epoxyketones have improved CNS drug properties than their linear counterparts and offer promising potential as an AD drug candidate.

Preparation and biological evaluation of soluble tetrapeptide epoxyketone proteasome inhibitors

A series of novel tetrapeptidyl epoxyketone inhibitors of 20S proteasome was designed and synthesized. To fully understand the SAR, various groups at R1, R2, R3, R4 and R5 positions, including aromatic and aliphatic substituents were designed, synthesized and biologically assayed. Based on the enzymatic results, seven compounds were selected to evaluate their cellular activities and soluble compound 36 showed strong potency against human multiple myeloma (MM) cell lines. Microsomal stability results indicated that compound 36 was more stable in mice, rat and human microsomes than marketed carfilzomib. The in vivo activities of this compound were evaluated with the xenograft mice models of MM cell lines ARH77 and RPMI-8226 with luciferase expression and the T/C value of the two models were 49.5% and 37.6%, respectively. To evaluate the potential cardiovascular toxicity, inhibition of hERG ion channel in HEK293 cells by compound 36 and carfilzomib was carried out. The results indicated that 36 had no binding affinity for the hERG ion channel while carfilzomib could bind it with IC50 of 92.1 μM.